Journal
PHARMACEUTICALS
Volume 14, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/ph14121276
Keywords
beta-blockers; carvedilol; matrix metalloproteinase-2; ischemia-reperfusion injury; isolated heart perfusion
Categories
Funding
- Polish State Committee for Scientific Research [N401 166 32/3235]
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The study showed that carvedilol improved cardiac mechanical function and reduced MMP-2 activation and release in myocardial ischemia-reperfusion injury, suggesting a cardioprotective effect mediated by inhibiting MMP-2 activation.
Matrix metalloproteinase 2 (MMP-2) is activated in hearts upon ischemia-reperfusion (IR) injury and cleaves sarcomeric proteins. It was shown that carvedilol and nebivolol reduced the activity of different MMPs. Hence, we hypothesized that they could reduce MMPs activation in myocytes, and therefore, protect against cardiac contractile dysfunction related with IR injury. Isolated rat hearts were subjected to either control aerobic perfusion or IR injury: 25 min of aerobic perfusion, followed by 20 min global, no-flow ischemia, and reperfusion for 30 min. The effects of carvedilol, nebivolol, or metoprolol were evaluated in hearts subjected to IR injury. Cardiac mechanical function and MMP-2 activity in the heart homogenates and coronary effluent were assessed along with troponin I content in the former. Only carvedilol improved the recovery of mechanical function at the end of reperfusion compared to IR injury hearts. IR injury induced the activation and release of MMP-2 into the coronary effluent during reperfusion. MMP-2 activity in the coronary effluent increased in the IR injury group and this was prevented by carvedilol. Troponin I levels decreased by 73% in IR hearts and this was abolished by carvedilol. Conclusions: These data suggest that the cardioprotective effect of carvedilol in myocardial IR injury may be mediated by inhibiting MMP-2 activation.
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